Martin H. Freeman Lecture Series

Professor Pablo Sobrado, Ph.D., Virginia Tech, will give a lecture titled, “Targeting novel flavin-dependent enzymes for the treatment of fungal, parasitic, and bacterial infections”

Iron is an essential nutrient for microbial grown as it is required for a large heme-dependent
and non-heme enzymatic reactions. Microbes acquire iron from their environment by heme
assimilation, reductive iron transport, and by using iron-binding molecules known as
siderophores. In Aspergillus fumigatus and in several bacteria including Mycobacterium
tuberculosis, siderophore biosynthesis is essential for virulence. Siderophores and their
biosynthetic enzymes are absent in humans. Thus, enzymes involved in the biosynthesis of
siderophore are ideal drug targets. Similarly, cell wall biosynthesis in bacterial and fungi have
been validated as a target for the development of antibiotics. This lecture will focus on the
studies of flavin-dependent enzymes involved in the biosynthesis of the cell wall and
siderophores in M. tuberculosis and A. fumigatus. Specifically, our work focuses on Nmonooxygenases
and UDP-galactopyranose mutases. Our approach includes biochemical,
structural, and computational studies that have allowed the characterization of the mechanism
of oxygen activation, covalent flavin intermediates, and cofactor associated catalysis. The
development of a high-throughput screening assay and identification of inhibitors will also be
presented.

Sponsored by the Chemistry & Biochemistry Department and the Center for Comparative Studies in Race and Ethnicity